Surgical sutures find common use in a broad range of medical procedures, often, but not exclusively, to hold skin, internal organs, blood vessels and all other tissues of the human body together after they have been severed by injury or surgery. In addition to serving as tissue fasteners, sutures and other elongate, thread-like medical devices can serve as a tissue scaffold or structural support for or during the growth of new tissue at a target tissue site, such as in tendon repair.
Sutures are available in a wide variety of forms, from monofilament to multi-filament to woven and braided filament construction, as a separate thread-like material or as a one-piece unit combined with a needle. They may be fabricated from a wide variety of biocompatible materials, ranging from non-absorbable materials such as cellulose (cotton, linen), protein-cellulose (silk), processed collagen (cat gut), nylon, polyester, polypropylene, aromatic polyamides (“aramid”), polytetraflourethylene, steel, copper, silver, aluminum, various alloys and the like, including many proprietary polymers and composites, to bioabsorbable (or biodegradable or bioerodible) synthetic materials, such as polymers and copolymers of glycolic and lactic acid.1234 Use of the latter—bioabsorbable materials—is often preferred as it avoids the need for additional surgical procedures (and the biological disruption associated therewith) to remove the suture. 1 Middleton, John et al., “Synthetic Biodegradable Polymers as Medical Devices”, Medical Plastics and Biomaterials Magazine (March, 1998).2 Shalaby, W et al., “Absorbable and biodegradable polymers”, CRC Press, ISBN:0849314844 (2003).3 Kotwal V B et al., “Biodegradable polymers: Which, when and why?”, Indian J Pharm Sci, 69 (5): 616-625 (2007).4 U.S. Pat. No. 6,838,493 to Williams et al. (2005).
In addition to being biocompatible, preferred suture materials should have good tensile strength, be compatible with a means of termination of the ends (such as tying or knotting), and be able to pass through the tissue during stitching with a minimum of friction or abrasion. Also, in cases where the suture passes through the skin or other barriers where fluid seepage could be an issue, a suture having reduced wicking properties, for example one having hydrophobic surface properties, is preferred. But apart from these desirable handling properties, it is also desirable that a suture, a material that is of necessity perceived by the immune system as “foreign”, not induce an inflammatory response or foster infection. Even more preferable are sutures that actively prevent or inhibit inflammation and infection, that not only close wounds but actively contribute to full healing. For example, in addition to providing structural support to wounded tissue, it is also desirable for a tissue scaffold to interact with adhering and invading cells and effectively guide cellular growth and development of new tissue, for example by releasing bioactive molecules such growth factors and cytokines [see Tessmar, Joerg et al., “Matrices and Scaffolds for Protein Delivery in Tissue Engineering”, Advanced Drug Delivery Reviews, 59 (4-5): 274-291 (May, 2007), incorporated by reference herein].
When selection of base materials and particular construction do not provide all the desired properties, it is known in the art to coat sutures with materials that achieve additional benefits, such as, but not limited to antimicrobial properties, tribologic properties, biocompatibility properties and properties to promote tissue growth or repair. Of particular interest is the inclusion in the suture coating of bioactive molecules, such as growth factors. For example, the use of sutures coated with a biodegradable matrix of various growth factor molecules has been shown to result in improved tissue regeneration at the application site [Dines, Joshua et al., “Biologics in Shoulder Surgery: Suture Augmentation and Coating to Enhance Tendon Repair”, Techniques in Orthopaedics: Biologics in Shoulder Surgery, vol. 22(1):20-25, (March 2007)]. However, while selected growth factors introduced from synthetic production have proven to have benefit, they are costly to produce and may provide adverse reactions in the patient. In addition, the selected mix of components may not have the requisite range of therapeutic activity associated with endogenous tissues and fluids.
As for endogenous materials, graft materials such as bone marrow and adipose tissues, as well as particular components isolated therefrom, such as growth factors and stem or progenitor cells, also find utility in the context of sutures and tissue scaffolds. In contrast to synthetic materials, the mechanisms and modalities of which are often not fully understood, transplant of endogenous tissues, cells and molecules is known to result in a symbiotic, synergistic effect in the promotion of tissue growth. While transplant and graft materials may be obtained from an intended recipient (autografts) or a matched donor (allografts), the former has several distinct advantages such as inherent biocompatibility, ready access and availability and reduced cost.
In the context of graft materials, stem cells are of particular interest, possessing not only the ability to differentiate into a broad range of tissues but also the ability to trigger other biological processes, sending chemical signals that affect the differentiation of other cells, the recruitment of cells to a specific tissue region and/or the modulation of the immunoregulatory system (thereby facilitating rapid healing and possessing the potential additional benefits of reduced swelling and reduced scar tissue formation).
While the art is replete with examples of sutures provided with such therapeutic and/or bioactive materials (see, for example, U.S. Pat. No. 6,264,675 to Brotz et al. as well as U.S. Patent Publication 2006/0047312 to Olmo et al., 2008/0171972 to Stopek et al., all of which are incorporated by reference herein), the technology in this area is often focused on surface coatings, particularly those that afford the surface of the suture with either antimicrobial properties or a limited number of predetermined types of bioactive molecules, such as specific growth factors, which have been produced in a sterile production environment, often by recombinant techniques. However, such prefabricated synthetic coating systems often fail in the context of a biological environment, with the coating of interest either being substantially removed in the course of insertion (e.g., wiped or stripped through contact with neighboring tissue) or rapidly dispersed after introduction. Rarely is a sufficient concentration and density of bioactive material maintained at the target site over the requisite period of time needed for the suture (and the bioactive material associated therewith) to exert its beneficial effect. Though this effect may be countered by providing the suture surface with an overabundance of bioactive material, high local concentrations of bioactive material can result in deleterious, even toxic effects. Moreover, given the high cost of manufacture for certain bioactive materials, particularly natural and synthetic growth factors, this is not a cost effective solution.
In addition to the above-noted disadvantages, the prefabricated coating systems also cannot readily be adapted for use with transplant and graft materials, whether extracted from an intended recipient (autografts) or a matched donor (allografts). Presently available options for delivery of graft material generally involve either the direct injection of the material into an area of interest or the material is injected into to a bone graft or bone graft substitute prior to insertion; however, in either case, there is typically no system to immobilize the material in the area of interest.
Thus, the present invention addresses the need in the art for the controlled, long-term delivery of bioactive materials of interest, such as stem cells and/or therapeutic agents, to target tissue sites by integrating such materials within surgical fasteners and tissue scaffolds (generically referred to herein as “sutures”). The present invention not only provides for the capture and delivery of such bioactive molecules, but also provides unique configurations that facilitate the utilization of extracted tissues and fluid, whether from the intended recipient (i.e., autologous transplant materials) or a selected donor organism (i.e., allogenic, homologous or heterologous transplant materials), as well as materials that are synthetically produced or produced from cell cultures (recombinant transplant materials). In particular, embodiments of the medical device constructs, precursors, kits and packaging systems of the present invention have unique and valuable advantages over current art, including: (i) bioactive material extracted from the patient can be inserted into an interior core of a suture construct by medical personnel (as opposed to being remotely manufactured in a prefabricated state); (ii) stem and progenitor cells and other cells of interest can be immobilized at the point of interest, in proximity to other materials of value and within an exterior sheath afforded with the necessary permeability and biodegradability; and (iii) biodegradable particles containing bioactive materials can be incorporated in the interior core in a manner where the materials are immobilized without affecting the overall flexibility of the assembled suture.